Diabetes insipidus


Diabetes insipidus
Diabetes insipidus
Classification and external resources

Vasopressin
ICD-10 E23.2 N25.1
ICD-9 253.5 588.1
OMIM 304800 125800
DiseasesDB 3639
MedlinePlus 000377
Central000460
Congenital
000461
Nephrogenic 000511
eMedicine med/543 ped/580
MeSH D003919

Diabetes insipidus (DI) is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause. The most common type in humans is central DI, caused by a deficiency of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). The second common type of DI is nephrogenic diabetes insipidus, which is caused by an insensitivity of the kidneys to ADH. It can also be an iatrogenic artifact of drug use.

Although they have a common name, diabetes mellitus and diabetes insipidus are two entirely separate conditions with unrelated mechanisms. Both cause large amounts of urine to be produced (polyuria), and the term diabetes is derived from the Greek name for this symptom. However, diabetes insipidus is either a problem with the production of antidiuretic hormone (cranial diabetes insipidus) or kidney's response to antidiuretic hormone (nephrogenic diabetes insipidus), whereas diabetes mellitus causes polyuria via a process called osmotic diuresis, due to the high blood sugar leaking into the urine and taking excess water along with it.

The incidence of diabetes insipidus in the general population is 3 in 100,000.[1] The name refers to the inability to retain fluid (diabetes = passing [water] through) and the lack of sugar in the urine (insipidus = tasteless).

Contents

Signs and symptoms

Excessive urination and extreme thirst (especially for cold water and sometimes ice or ice water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine does not contain glucose and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity. Signs of dehydration may also appear in some individuals since the body cannot conserve much (if any) of the water it takes in.

The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.

Diagnosis

In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops). Urinalysis demonstrates a dilute urine with a low specific gravity. Urine osmolarity and electrolyte levels are typically low.

A fluid deprivation test helps determine whether DI is caused by:

  1. excessive intake of fluid (primary polydipsia)
  2. a defect in ADH production
  3. a defect in the kidneys' response to ADH

This test measures changes in body weight, urine output, and urine composition when fluids are withheld and as dehydration occurs. The body's normal response to dehydration is to concentrate urine and conserve water, so urine becomes more concentrated and urination becomes less frequent. Those with DI continue to urinate large amounts of dilute urine in spite of not drinking any fluids. In primary polydipsia, the urine osmolality should increase and stabilize at above 280 Osm/kg with fluid restriction, while a stabilization at a lower level indicates diabetes insipidus.[2] Stabilization in this test means, more specifically, when the hourly increase in osmolality is less than 30 Osm/kg per hour for at least 3 hours.[2] Sometimes measuring blood levels of ADH during this test is also necessary, but is more time consuming to perform.[2]

To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.

If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma, or histiocytosis, syphilis, tuberculosis or other tumor or granuloma) is affecting pituitary function. Most people with this form have either experienced past head trauma or have stopped ADH production for an unknown reason.

Habit drinking (in its severest form termed psychogenic polydipsia) is the most common imitator of diabetes insipidus at all ages. While many adult cases in the medical literature are associated with mental disorders, most patients with habit polydipsia have no other detectable disease. The distinction is made during the water deprivation test, as some degree of urinary concentration above isosmolar is usually obtained before the patient becomes dehydrated.

Pathophysiology

Electrolyte and volume homeostasis is a complex mechanism that balances the body's requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.

The regulation of urine production occurs in the hypothalamus, which produces ADH in the supraoptic and paraventricular nuclei. After synthesis, the hormone is transported in neurosecretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitary gland where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.

The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubules, specifically it acts on proteins called aquaporins and more specifically aquaporin 2 in the following cascade; ADH (aka argenine vasopressin-AVP) produced in the hypothalmus and stored in the posterior pituitary. When released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing cyclic AMP, which couples with protein kinase A stimulating transcription of the aquaporin 2 channel stored in the cytoplasm of the distal convoluted tubules and collecting ducts into the apical membrane. These transcripted channels allow water into the collecting duct cells. The increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.

Hereditary forms of diabetes insipidus account for less than 10% of the cases of diabetes insipidus seen in clinical practice.[3]

Classification

There are several forms of DI:

Neurogenic

Neurogenic diabetes insipidus, more commonly known as central diabetes insipidus, is due to a lack of vasopressin production in the brain.

Nephrogenic

Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to vasopressin.

Dipsogenic

Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus.[4] This defect results in an abnormal increase in thirst and fluid intake that suppresses vasopressin secretion and increases urine output. Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.

Gestational

Gestational DI only occurs during pregnancy. During pregnancy, all women produce vasopressinase in the placenta, which breaks down ADH. Gestational DI is thought to occur with excessive vasopressinase production.[5]

Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.

Diabetes insipidus is also associated with some serious diseases of pregnancy, including pre-eclampsia, HELLP Syndrome and acute fatty liver of pregnancy. These cause diabetes insipidus by activating hepatic vasopressinase. It is important to consider these diseases if a woman presents with diabetes insipidus in pregnancy, because their treatments require delivery of the baby before the disease will improve. Failure to treat these diseases promptly can lead to maternal or perinatal mortality.

Treatment

Central DI and gestational DI respond to desmopressin. Carbamazepine, an anti-convulsive medication, has also had some success in this type of DI. Also gestational DI tends to abate on its own 4 to 6 weeks following labour, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.

Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic hydrochlorothiazide (a thiazide diuretic) or indomethacin can improve nephrogenic diabetes insipidus. Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia. It seems paradoxical to treat an extreme diuresis with a diuretic but the thiazide diuretics will decrease distal convoluted tubule reabsorption of sodium and water, thereby causing diuresis. This decreases plasma volume, thus lowering GFR and enhancing the absorption of sodium and water in the proximal nephron. Less fluid reaches the distal nephron so overall fluid conservation is obtained.

Lithium-induced nephrogenic DI may be effectively managed with the administration of amiloride, a potassium-sparing diuretic often used in conjunction with thiazide or loop diuretics. Clinicians have been aware of lithium toxicity for many years and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus. However, recently amiloride has been shown to be a successful treatment for this condition.[6]

References

  1. ^ [1] Saborio, P.; Tipton, G. A.; Chan, J. C. M. (2000). "Diabetes Insipidus". Pediatrics in Review 21 (4): 122–129. doi:10.1542/pir.21-4-122. PMID 10756175.  edit
  2. ^ a b c Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6. 
  3. ^ Fujiwara, T. M.; Bichet, D. (2005). "Molecular Biology of Hereditary Diabetes Insipidus". Journal of the American Society of Nephrology 16 (10): 2836–2846. doi:10.1681/ASN.2005040371. PMID 16093448.  edit [2]
  4. ^ Perkins RM, Yuan CM, Welch PG (March 2006). "Dipsogenic diabetes insipidus: report of a novel treatment strategy and literature review". Clin. Exp. Nephrol. 10 (1): 63–7. doi:10.1007/s10157-005-0397-0. PMID 16544179. 
  5. ^ Kalelioglu I, Kubat Uzum A, Yildirim A, Ozkan T, Gungor F, Has R (2007). "Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery". Pituitary 10 (1): 87–93. doi:10.1007/s11102-007-0006-1. PMID 17308961. 
  6. ^ Finch CK, Kelley KW, Williams RB. Treatment of lithium-induced diabetes insipidus with amiloride. Pharmacotherapy. 2003 Apr;23(4):546-50. PMID 12680486

Further reading

  • The public domain document "Diabetes Insipidus", NIH Publication No. 01-4620, December 2000.

External links


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Look at other dictionaries:

  • Diabetes insipidus — diabetes di a*be tes, n. [NL., from Gr. ?, fr. ? to pass or cross over. See {Diabase}.] (Med.) Any of several diseases which is attended with a persistent, excessive discharge of urine; when used without qualification, the term usually refers to… …   The Collaborative International Dictionary of English

  • diabetes insipidus — diabetes di a*be tes, n. [NL., from Gr. ?, fr. ? to pass or cross over. See {Diabase}.] (Med.) Any of several diseases which is attended with a persistent, excessive discharge of urine; when used without qualification, the term usually refers to… …   The Collaborative International Dictionary of English

  • diabetes insipidus — diabetes di a*be tes, n. [NL., from Gr. ?, fr. ? to pass or cross over. See {Diabase}.] (Med.) Any of several diseases which is attended with a persistent, excessive discharge of urine; when used without qualification, the term usually refers to… …   The Collaborative International Dictionary of English

  • diabetes insipidus — [in sip′i dəs] n. 〚ModL, lit., insipid diabetes〛 a disorder caused by a pituitary deficiency and characterized by the heavy discharge of urine and intense thirst * * * Endocrine disorder causing extreme thirst and excessive production of very… …   Universalium

  • diabetes insipidus — diabetes in·sip·i·dus in sip əd əs n a disorder that is caused by insufficient secretion of vasopressin by the pituitary gland or by a failure of the kidneys to respond to circulating vasopressin and that is characterized by intense thirst and by …   Medical dictionary

  • diabetes insipidus — [in sip′i dəs] n. [ModL, lit., insipid diabetes] a disorder caused by a pituitary deficiency and characterized by the heavy discharge of urine and intense thirst …   English World dictionary

  • diabetes insipidus — diabetes insipidus. См. несахарный диабет. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • Diabetes insipidus — Klassifikation nach ICD 10 E23.2 Hypophysärer Diabetes insipidus N25.1 Renaler Diabetes insipidus …   Deutsch Wikipedia

  • Diabetes insipidus — ADH Mangel * * * Diabetes insipidus   [lateinisch insipidus »unschmackhaft« (hier im Hinblick auf den Harn: ohne den charakteristischen süßen Geschmack wie bei Diabetes mellitus)] der, , Wasserharnruhr, Stoffwechselstörung mit abnorm gesteigerter …   Universal-Lexikon

  • diabetes insipidus — noun a rare form of diabetes resulting from a deficiency of vasopressin (the pituitary hormone that regulates the kidneys); characterized by the chronic excretion of large amounts of pale dilute urine which results in dehydration and extreme… …   Useful english dictionary


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